As used herein, "LDPE" means low density polyethylene.
Prostaglandins have notoriously low water solubility, and are generally unstable. Attempts have been made to solubilize and stabilize various prostaglandins by complexing them with different cyclodextrins. See, for example: EP 330 511 A2 (Ueno et al.) and EP 435 682 A2 (Wheeler). These attempts have met with varying success.
Surfactants and/or solubilizers have been used with other types of drugs having low water solubility. However, the addition of surfactants and/or solubilizers may enhance or adversely affect the chemical stability of drug compounds. See Surfactant Systems, Their Chemistry, Pharmacy, and Biology, (eds. Attwood et al.), Chapman and Hall, New York, 1983, Ch. 11, particularly pp. 698-714.
The use of non-ionic surfactants, such as polyethoxylated castor oils, as solubilizing agents is known. See, for example, U.S. Pat. No. 4,960,799 (Nagy).
The use of non-ionic surfactants such as polyethoxylated castor oils in stable emulsions is also known. U.S. Pat. No. 4,075,333 (Josse) discloses stable, intravenous emulsion formulations of vitamins. El-Sayed et al., Int. J. Pharm., 13:303-12 (1983) discloses stable oil-in-water emulsions of an antineoplastic drug. U.S. Pat. No. 5,185,372 (Ushio et al.) discloses topically administrable ophthalmic formulations of vitamin A which are stable preparations in which a non-ionic surfactant is used to form an emulsion of vitamin A in an aqueous medium.
U.S. Pat. No. 5,631,287 (Schneider) discloses storage-stable prostaglandin compositions containing a chemically stabilizing amount of a polyethoxylated castor oil.
Presently, there are only two commercially available ophthalmic multidose prostaglandin products, Xalatan.TM. (latanoprost solution; Upjohn) and Rescula.TM. (isopropyl unoprostone; Fujisawa). Xalatan.TM. is packed in a polyethylene (LDPE) container. According to the package insert, this product must be stored under refrigeration at 2-80.degree. C. until opened. Once opened, the container may be stored at room temperature up to 25.degree. C. for six weeks.
Rescula.TM. is also packaged in a polyethylene (LDPE) container.